Influence of the rate of 7,12-dimethylbenz[a]anthracene metabolic activation, in vivo, on its binding to epidermal DNA and skin carcinogenesis.
The effects of skin pretreatment of two strains of Swiss mice, NMRI and CF1, with beta-naphthoflavone on epidermal tumors induced by 7,12-dimethylbenz[a]anthracene (DMBA) have been studied. NMRI Swiss strain exhibits a natural high sensitivity to the carcinogenic effect of the hydrocarbon, and the pretreatment of mice be beta-naphthoflavone leads to a large decrease of the formation of tumors. In contrast, CF1 Swiss mice exhibit a very low sensitivity to the carcinogenic effect of DMBA and a dramatic increase of the tumorigenicity occurs when the animals are pretreated by the inducer. Aryl hydrocarbon hydroxylase activity in skin homogenates of control and differently induced NMRI and CF1 mice has been measured and compared to (a) the kinetics of disappearance of [3H]DMBA from skin in control and beta-naphthoflavone-treated mice and (b) the kinetics of the covalent binding of the radioactive hydrocarbon to skin epidermal DNA (in control an beta-naphthoflavone-treated mice). The comparison between these three parameters and the tumorigenicity experiments seem to indicate that an optimal rate of DMBA metabolic activation exists which corresponds to a high level of skin tumors correlated with DNA binding of the polycyclic hydrocarbon. These data might explain some conflicting results which have been reported on the effect of inducers of aryl hydrocarbon hydroxylases on tumor induction by polycyclic aromatic hydrocarbons.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000378:metabolism*; D000818:Animals; D001551:Benz(a)Anthracenes / Q000378:metabolism*; D001711:Biotransformation; D004247:DNA / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051379:Mice; D009374:Neoplasms, Experimental / Q000139:chemically induced; D012867:Skin / Q000378:metabolism*; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000378:metabolism
D001551:Benz(a)Anthracenes; D015127:9,10-Dimethyl-1,2-benzanthracene; D004247:DNA